Butorphanol is a drug that is classified into an opioid-based analgesic and has a molecular structure of morphinan skeleton. An injection containing butorphanol tartrate for postoperative analgesia has been utilized. As such butorphanol, N-cyclobutylmethyl-3,14-dihydroxymorphinan is disclosed in U.S. Pat. No. 3,775,414 (PTL 1) and U.S. Pat. No. 3,819,635 (PTL 2), for example.
In addition, an in vitro study on transdermal permeation of butorphanol has been reported in M. Svozil et al., Drug. Dev. Ind. Pharm., 33(5), 559-67 (2007) (NPL 1). NPL 1 discloses that butorphanol is an effective drug as a drug for transdermal therapeutic system, and that transkarbam 12, laurocapram (which is the same as AZONE (trade mark)), and isopropylmyristate have been studied as transdermal absorption enhancers, and transkarbam is particularly suitable.
Meanwhile, International Publication No. 2005/102393 (PTL 3) discloses a pressure-sensitive adhesive composition for transdermal absorption, containing a drug, a transdermal absorption enhancer, and a polyvinylpyrrolidone. PTL 3 states that the drug is not particularly limited as long as the drug is one used in general, and illustrates and lists 32 drug classes, such as hypnotic and sedative agents, antipyretic, anti-inflammatory, and analgesic agents, steroidal anti-inflammatory agents, excitants and stimulants, neuropsychiatric agents, and agents for urinary organs, and a large number of drugs over a wide variety for each of these drug classes. As one of the antipyretic, anti-inflammatory, and analgesic agents among them, butorphanol tartrate is given. In addition, as the transdermal absorption enhancer, a wide variety of compounds are illustrated, such as carboxylic acids having 2 to 7 carbon atoms, fatty acids having 6 to 20 carbon chains, fatty acid esters or ethers, aromatic organic acids, aromatic alcohols, aromatic organic acid esters or ethers, lactylic esters, acetic esters, monoterpene-based compounds, sesquiterpene-based compounds, and aliphatic alcohols are given as one kind of them. However, PTL 3 substantially describes no pharmaceutical preparation containing butorphanol, and neither discloses nor suggests at all a combination of butorphanol and a particular transdermal absorption enhancer, or the skin permeability and crystal precipitation of butorphanol.